Department of Digestive Endoscopy, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
Department of General Medicine, The General Hospital of China National Petroleum Corporation in Jilin, Jilin 132021, P.R. China.
Oncol Rep. 2018 Mar;39(3):1494-1504. doi: 10.3892/or.2017.6171. Epub 2017 Dec 20.
Gastric cancer (GC) is the fifth most commonly diagnosed malignant disease and the third leading cause of cancer‑related deaths worldwide. Recently, numerous microRNAs (miRNAs) have been determined to contribute to GC initiation and progression, suggesting that miRNAs may be developed as effective diagnostic and prognostic molecular biomarkers and can be investigated as therapeutic targets for patients with this disease. Therefore, further investigation of the miRNAs involved in GC development represents an opportunity to improve the prognosis of GC patients. miRNA‑454 (miR‑454) is abnormally expressed in multiple types of human cancer. However, the expression pattern, biological roles and underlying mechanism of miR‑454 in GC remain unclear and require further investigation. In the present study, we assessed miR‑454 expression in GC tissues and cell lines. We also explored the effects of miR‑454 on the biological behaviours of tumour cells and the underlying molecular mechanisms of miR‑454. The results revealed that miR‑454 was significantly downregulated in GC tissues and cell lines. Low miR‑454 expression was positively associated with lymph node metastasis, invasive depth and TNM stage. Additionally, upregulation of miR‑454 inhibited cell proliferation and invasion and induced the apoptosis of the GC cells. Subsequently, mitogen‑activated protein kinase 1 (MAPK1) was identified as a direct target of miR‑454. MAPK1 was upregulated in GC tissues and was found to be negatively correlated with the miR‑454 expression level. Downregulation of MAPK1 also suppressed GC cell proliferation and invasion and increased apoptosis, thereby resembling the suppressive effects of miR‑454 overexpression in GC. Moreover, upregulation of MAPK1 reversed the tumour‑suppressive effects of miR‑454 in GC. Collectively, our data demonstrated that miR‑454 may play tumour‑suppressing roles in GC through the regulation of MAPK1, suggesting that miR‑454 may be a novel biomarker and therapeutic target for patients with this disease.
胃癌（GC）是全球第五种最常见的恶性疾病，也是癌症相关死亡的第三大主要原因。最近，大量的 microRNAs（miRNAs）被确定与 GC 的发生和发展有关，这表明 miRNAs 可能被开发为有效的诊断和预后分子生物标志物，并可作为该疾病患者的治疗靶点进行研究。因此，进一步研究参与 GC 发展的 miRNAs 代表了改善 GC 患者预后的机会。miRNA-454（miR-454）在多种人类癌症中异常表达。然而，miR-454 在 GC 中的表达模式、生物学作用和潜在机制尚不清楚，需要进一步研究。在本研究中，我们评估了 GC 组织和细胞系中的 miR-454 表达。我们还探讨了 miR-454 对肿瘤细胞生物学行为的影响及其潜在的分子机制。结果表明，miR-454 在 GC 组织和细胞系中显著下调。低 miR-454 表达与淋巴结转移、浸润深度和 TNM 分期呈正相关。此外，上调 miR-454 抑制了 GC 细胞的增殖和侵袭，并诱导了 GC 细胞的凋亡。随后，丝裂原活化蛋白激酶 1（MAPK1）被鉴定为 miR-454 的直接靶标。MAPK1 在 GC 组织中上调，并发现与 miR-454 表达水平呈负相关。下调 MAPK1 也抑制了 GC 细胞的增殖和侵袭，并增加了凋亡，从而类似于 miR-454 过表达在 GC 中的抑制作用。此外，上调 MAPK1 逆转了 miR-454 在 GC 中的肿瘤抑制作用。综上所述，我们的数据表明，miR-454 通过调节 MAPK1 可能在 GC 中发挥肿瘤抑制作用，表明 miR-454 可能是该疾病患者的一种新的生物标志物和治疗靶点。
